Effect of S-Ketamine on Postoperative Nausea and Vomiting in Patients Undergoing Video-Assisted Thoracic Surgery: A Randomized Controlled Trial.

Purpose: Postoperative nausea and vomiting (PONV) frequently occur in patients after surgery. In this study, the authors investigated whether perioperative S-ketamine infusion could decrease the incidence of PONV in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy. Patients and Methods: This prospective, randomized, double-blinded, controlled study was conducted a total of 420 patients from September 2021 to May 2023 at Xuzhou Central Hospital in China, who underwent elective VATS lobectomy under general anesthesia with tracheal intubation. The patients were randomly assigned to either the S-ketamine group or the control group. The S-ketamine group received a bolus injection of 0.5 mg/kg S-ketamine and an intraoperative continuous infusion of S-ketamine at a rate of 0.25 mg/kg/h. The control group received an equivalent volume of saline. All patients were equipped with patient-controlled intravenous analgesia (PCIA), with a continuous infusion rate of 0.03 mg/kg/h S-ketamine in the S-ketamine group or 0.03 µg/kg/h sufentanil in the control group. The primary outcome was the incidence of PONV. Secondary outcomes included perioperative opioid consumption, hemodynamics, postoperative pain, and adverse events. Results: The incidence of PONV in the S-ketamine group (9.7%) was significantly lower than in the control group (30.5%). Analysis of perioperative opioid usage revealed that remifentanil usage was 40.0% lower in the S-ketamine group compared to the control group (1414.8 µg vs 2358.2 µg), while sufentanil consumption was 75.2% lower (33.1 µg vs 133.6 µg). The S-ketamine group demonstrated better maintenance of hemodynamic stability. Additionally, the visual analogue scale (VAS) scores on postoperative day 1 (POD-1) and postoperative day 3 (POD-3) were significantly lower in the S-ketamine group. Finally, no statistically significant difference in other postoperative adverse reactions was observed between the two groups. Conclusion: The results of this trial indicate that perioperative S-ketamine infusion can effectively reduce the incidence of PONV in patients undergoing VATS lobectomy.

Analysis of preoperative computed tomography radiomics and clinical factors for predicting postsurgical recurrence of papillary thyroid carcinoma.

BACKGROUND: Postsurgical recurrence is of great concern for papillary thyroid carcinoma (PTC). We aim to investigate the value of computed tomography (CT)-based radiomics features and conventional clinical factors in predicting the recurrence of PTC. METHODS: Two-hundred and eighty patients with PTC were retrospectively enrolled and divided into training and validation cohorts at a 6:4 ratio. Recurrence was defined as cytology/pathology-proven disease or morphological evidence of lesions on imaging examinations within 5 years after surgery. Radiomics features were extracted from manually segmented tumor on CT images and were then selected using four different feature selection methods sequentially. Multivariate logistic regression analysis was conducted to identify clinical features associated with recurrence. Radiomics, clinical, and combined models were constructed separately using logistic regression (LR), support vector machine (SVM), k-nearest neighbor (KNN), and neural network (NN), respectively. Receiver operating characteristic analysis was performed to evaluate the model performance in predicting recurrence. A nomogram was established based on all relevant features, with its reliability and reproducibility verified using calibration curves and decision curve analysis (DCA). RESULTS: Eighty-nine patients with PTC experienced recurrence. A total of 1218 radiomics features were extracted from each segmentation. Five radiomics and six clinical features were related to recurrence. Among the 4 radiomics models, the LR-based and SVM-based radiomics models outperformed the NN-based radiomics model (P = 0.032 and 0.026, respectively). Among the 4 clinical models, only the difference between the area under the curve (AUC) of the LR-based and NN-based clinical model was statistically significant (P = 0.035). The combined models had higher AUCs than the corresponding radiomics and clinical models based on the same classifier, although most differences were not statistically significant. In the validation cohort, the combined models based on the LR, SVM, KNN, and NN classifiers had AUCs of 0.746, 0.754, 0.669, and 0.711, respectively. However, the AUCs of these combined models had no significant differences (all P > 0.05). Calibration curves and DCA indicated that the nomogram have potential clinical utility. CONCLUSIONS: The combined model may have potential for better prediction of PTC recurrence than radiomics and clinical models alone. Further testing with larger cohort may help reach statistical significance.

FoxO and rotund form a binding complex governing wing polyphenism in planthoppers.

Wing polyphenism is found in a variety of insects and offers an attractive model system for studying the evolutionary significance of dispersal. The Forkhead box O (FoxO) transcription factor (TF) acts as a wing-morph switch that directs wing buds developing into long-winged (LW) or short-winged morphs in wing-dimorphic planthoppers, yet the regulatory mechanism of the FoxO module remains elusive. Here, we identified the zinc finger TF rotund as a potential wing-morph regulator via transcriptomic analysis and phenotypic screening in the brown plathopper, Nilaparvata lugens. RNA interference-mediated knockdown of rotund antagonized the LW development derived from in the context of FoxO depletion or the activation of the insulin/insulin-like growth factor signaling cascade, reversing long wings into intermediate wings. In vitro binding assays indicated that rotund physically binds to FoxO to form the FoxO combinatorial code. These findings broaden our understanding of the complexity of transcriptional regulation governing wing polyphenism in insects.

Are There More Radiolucent Lines in Patients Who Underwent Total Knee Arthroplasty With or Without a Tourniquet During Cementation at 5 to 8 Years After Surgery?

BACKGROUND: This study investigated the presence and progression of radiolucent lines (RLLs) after cemented total knee arthroplasty (TKA) with or without tourniquet use. METHODS: There were 369 consecutive primary cemented TKAs with 5 to 8 years of follow-up. A tourniquet was used during component cementation in patients who underwent surgery from January 3, 2006, to March 31, 2010. No tourniquet was used from August 14, 2009, to October 14, 2014. There were 192 patients in the tourniquet group (TQ) and 177 patients in the no tourniquet group (NQ). Patient demographics, reoperations, and complications were recorded. RLLs were identified on anteroposterior, lateral, and skyline x-rays at 1, 2, and 5 to 8 years postoperatively using the modern knee society radiographic evaluation system. Demographics, reoperations, complications, and RLLs were compared. Age, sex, and body mass index were similar between groups. Mean tourniquet time in TQ was 11 minutes (range, 8 to 25). RESULTS: The presence of RLLs differed between groups, with 65% of TQ knees having RLLs under any part of the prostheses versus 46% of NQ knees (P < .001). The progression of RLL >2 mm occurred in 26.0% of knees in TQ and 16.7% of knees in NQ (P = .028). There were 13 TKAs that underwent subsequent revision surgery. There was no statistically or clinically significant difference in revision rate between groups (7 revisions in TQ, 6 in NQ, P = .66). CONCLUSION: Less RLLs were identified in NQ versus TQ. There were no statistically or clinically significant differences in revision rates between the NQ and TQ groups at 5 to 8 years.

High-Throughput Screening and Directed Evolution of Methionine Adenosyltransferase from Escherichia coli.

S-adenosyl-L-methionine (SAM) is the active form of methionine, which participates in various metabolic reactions and plays a vital role. It is mainly used as a precursor by three key metabolic pathways: trans-methylation, trans-sulfuration, and trans-aminopropylation. Methionine adenosyltransferase (MAT) is the only enzyme to produce SAM from methionine and ATP. However, there is no efficient and accurate method for high-throughput detection of SAM, which is the major obstacles of directed evolution campaigns for MAT. Herein, we established a colorimetric method for directed evolution of MAT based on detecting SAM by using glycine oxidase and glycine/sarcosine N-methyltransferase enzyme. Screening of MAT libraries revealed variant I303V/Q22R with 2.13-fold improved activity towards SAM in comparison to the wild type. Molecular dynamic simulation indicates that the loops more flexible and more conducive to SAM release.

A flavonol-derived fluorescent probe for highly specific and sensitive detection of hydrazine in actual environmental samples and living zebrafish.

Hydrazine (N2H4) is a significant chemical reagent and widely applied in industrial field, which can bring potential risk to environmental safety and human health due to its high toxicity and potential carcinogenicity. In this paper, a flavonol-derived fluorescent probe named TB-N2H4 was rationally developed for detecting N2H4 based on the excited intramolecular proton transfer (ESIPT) principle. TB-N2H4 exhibited a remarkable fluorescence turn-on response toward N2H4 with a large Stokes shift of 191 nm. Moreover, TB-N2H4 could selectively recognize N2H4 over other competitive analytes, and displayed high sensitivity toward N2H4 with a low detection limit of 0.117 µM. The sensing mechanism of the probe TB-N2H4 for N2H4 was confirmed by theoretical calculation and HRMS analysis. This probe was able to quantitatively determine N2H4 in environmental water and soil samples. Additionally, TB-N2H4 was also successfully utilized for real-time tracking of the distribution of N2H4 in living zebrafish.

Enhanced CT-based radiomics model to predict natural killer cell infiltration and clinical prognosis in non-small cell lung cancer.

Background: Natural killer (NK) cells are crucial for tumor prognosis; however, their role in non-small-cell lung cancer (NSCLC) remains unclear. The current detection methods for NSCLC are inefficient and costly. Therefore, radiomics represent a promising alternative. Methods: We analyzed the radiogenomics datasets to extract clinical, radiological, and transcriptome data. The effect of NK cells on the prognosis of NSCLC was assessed. Tumors were delineated using a 3D Slicer, and features were extracted using pyradiomics. A radiomics model was developed and validated using five-fold cross-validation. A nomogram model was constructed using the selected clinical variables and a radiomic score (RS). The CIBERSORTx database and gene set enrichment analysis were used to explore the correlations of NK cell infiltration and molecular mechanisms. Results: Higher infiltration of NK cells was correlated with better overall survival (OS) (P = 0.002). The radiomic model showed an area under the curve of 0.731, with 0.726 post-validation. The RS differed significantly between high and low infiltration of NK cells (P < 0.01). The nomogram, using RS and clinical variables, effectively predicted 3-year OS. NK cell infiltration was correlated with the ICOS and BTLA genes (P < 0.001) and macrophage M0/M2 levels. The key pathways included TNF-α signaling via NF-κB and Wnt/ß-catenin signaling. Conclusions: Our radiomic model accurately predicted NK cell infiltration in NSCLC. Combined with clinical characteristics, it can predict the prognosis of patients with NSCLC. Bioinformatic analysis revealed the gene expression and pathways underlying NK cell infiltration in NSCLC.

New insight into the current study of high tibial osteotomy: A bibliometric analysis.

BACKGROUND: To analyze global trends in focus and funding of research related to high tibial osteotomy (HTO) and to identify the 100 most cited articles in this field. METHODS: A Web of Science search was used to identify HTO publications in English-language scientific journals from January 1967 till February 3th, 2021. Results were filtered to the 100 most cited articles by reading the abstract or full-text paper. Information of these articles was recorded for further analysis. The 10 top-cited articles during the last 5 years and the 10 top-cited articles about HTO ranked by average citations per year were selected to predict research trends. RESULTS: In all, 48 out of the 100 top-cited articles were published between 2000 and 2010. The United States of America was the primary contributor (n = 29) followed by Germany (n = 17) and Japan (n = 11). The total number of citations per article ranged from 65 to 563, median 108, mean 135 (standard deviation = 84). The American Journal of Bone and Joint Surgery accounted for 23 out of the 100 top-cited articles. Koshino T was the most cited author (603 citations). The most frequently highlighted study theme was prognostic research. Patient-based clinical research was the dominant study design (85%). The majority of articles (48 out of 100) were level IV evidence with a mean of 141 (standard deviation = 97) citations. Top-cited articles in the last 5 years focused on open wedge osteotomy. CONCLUSION: Technical optimization of open wedge osteotomy has emerged as the main area of research in HTO. More specifically, recent publications focus on the surgical technology, cartilage repair and new fixation devices. Besides, papers with a high level of evidence are needed for the development of HTO.

Magnetic resonance imaging-based radiomics model for predicting radiation-induced temporal lobe injury in nasopharyngeal carcinoma after intensity-modulated radiotherapy.

BACKGROUND: To develop a model based on magnetic resonance imaging (MRI) radiomics and clinical features for predicting radiation-induced temporal lobe injury (RTLI) in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). METHODS: Two hundred and sixteen patients with NPC were retrospectively included. Radiomics features were extracted and selected. The logistic regression analysis was performed for prediction models construction. The area under the receiver operating characteristic curve (AUC) was calculated for performance evaluation. RESULTS: Three radiomics features were selected to construct the radiomics signature (AUC of 0.94 and 0.92). The clinical-radiomics model, integrating radiomics signature with T classification, achieved higher predictive performance in the training and validation cohorts (AUC of 0.95 and 0.93), as well as improved accuracy of the classification of RTLI outcomes (net reclassification improvement: 0.711; 95% CI: 0.57-0.86; p < 0.001). CONCLUSIONS: The clinical-radiomics model and radiomics signature both showed great performance in predicting RTLI in patients with NPC.

The transcription factor Zfh1 acts as a wing-morph switch in planthoppers.

Insect wing polyphenism is characterized by its ability to produce two or more distinct wing morphs from a single genotype in response to changing environments. However, the molecular basis of this phenomenon remains poorly understood. Here, we identified a zinc finger homeodomain transcription factor Zfh1 that acts as an upstream regulator for the development of long-winged (LW) or shorted-winged (SW) morphs in planthoppers. Knockdown of Zfh1 directs SW-destined nymphs to develop into LW morphs by down-regulating the transcriptional level of FoxO, a prominent downstream effector of the insulin/IGF signaling (IIS) pathway. The balance between transcriptional regulation via the Zfh1-FoxO cascade and post-translational regulation via the IIS-FoxO cascade provides a flexible regulatory mechanism for the development of alternative wing morphs. These findings help us understand how phenotypic diversity is generated by altering the activity of conserved proteins, and provide an extended framework for the evolution of wing morphological diversity in insects.

Functionalization of Se-Te Nanorods with Au Nanoparticles for Enhanced Anti-Bacterial and Anti-Cancer Activities.

The use of medical devices for therapeutic and diagnostic purpose is globally increasing; however, bacterial colonization on therapeutic devices can occur, causing severe infections in the human body. It has become an issue for public health. It is necessary to develop a nanomaterial based on photothermal treatment to kill toxic bacterial strains. Appropriately, high photothermal conversion and low-cost powerful photothermal agents have been investigated. Recently, gold nanocomposites have attracted great interest in biological applications. Here, we prepared rod-shaped Se-Te@Au nanocomposites of about 200 nm with uniform shape and surface-coated with gold nanoparticles for the first time showing high anti-bacterial and anti-cancer activities. Se-Te@Au showed proper structural consistency and natural resistance to bacterial and cancer cells. The strong absorption and high photothermal conversion efficacy made it a good photothermal agent material for the photothermal treatment of bacterial and cancer cells. The Se-Te@Au rod showed excellent anti-bacterial efficacy against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus, with highest recorded inhibition zones of 25 ± 2 mm and 22 ± 2 mm, respectively. More than 99% of both types of strains were killed after 5 min with a near-infrared (NIR) laser at the very low concentration of 48 µg/mL. The Se-Te@Au rod's explosion in HeLa cells was extensively repressed and demonstrated high toxicity at 100 µg/mL for 5 min when subjected to an NIR laser. As a result of its high photothermal characteristics, the exceptional anti-bacterial and anti-cancer effects of the Se-Te@Au rod are considerably better than those of other methods previously published in articles. This study could open a new framework for sterilization applications on the industrial level.

GaIIItriarylcorroles with push-pull substitutions: synthesis, electronic structure and biomedical applications.

Two A2B type H3corroles and two GaIIItriarylcorroles with carbazole substitutions at 10-positions were synthesized and characterized. An analysis of structure-property relationships of the corroles has been carried out by investigating the optical spectroscopy of the dyes to trends predicted in DFT and TD-DFT calculations. Interestingly, the photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) activity properties of the GaIIItriarylcorroles were determined against the MCF-7 breast cancer line, and Staphyloccocus aureus (S. aureus) and Escherichia coli (E. coli), respectively. The cationic G-2Q species exhibited the most favorable properties with an IC50 value of 7.8 µM against MCF-7 cells, and Log reduction values of 7.78 and 3.26 against planktonic S. aureus and E. coli at 0.5 and 10 µM, respectively.

Small-Molecule Photoacoustic Imaging Probe with Aggregation-Enhanced Amplitude for Real-Time Visualization of Acute Kidney Injury.

Acute kidney injury (AKI) has become a growing issue for patients with the extensive use of all kinds of drugs in clinic. Photoacoustic (PA) imaging provides a noninvasive and real-time imaging method for studying kidney injury, but it has inherent shortages in terms of high background signal and low detection sensitivity for exogenous imaging agents. Intriguingly, J-aggregation offers to tune the optical properties of the dyes, thus providing a platform for developing new PA probes with desired performance. In this study, a small-molecule PA probe (BDP-3) was designed and synthesized. We serendipitously discovered that BDP-3 can transform into renal clearable nanoaggregates under physiological conditions. The hydrodynamic diameter of the BDP-3 increased from 0.64 ± 0.11 to 3.74 ± 0.39 nm when the content of H2O increased from 40 to 90%. In addition, it was surprising that such a transforming process can significantly enhance its PA amplitude (2.06-fold). On this basis, PA imaging with BDP-3 was applied as a new method for the noninvasive detection of AKI induced by anticancer drugs, traditional Chinese medicine, and clinical contrast agents in animal models and exhibited higher sensitivity than the conventional serum index test, demonstrating great potential for further clinical diagnostic applications.

A MRI-based radiomics model predicting radiation-induced temporal lobe injury in nasopharyngeal carcinoma.

OBJECTIVES: To develop and validate a radiomics-based model for predicting radiation-induced temporal lobe injury (RTLI) in nasopharyngeal carcinoma (NPC) by pretreatment MRI of the temporal lobe. METHODS: A total of 216 patients with diagnosed NPC were retrospectively reviewed. Patients were randomly allocated to the training (n = 136) and the validation cohort (n = 80). Radiomics features were extracted from pretreatment contrast-enhanced T1- or fat-suppressed T2 weighted MRI. A radiomics signature was generated by the least absolute shrinkage and selection operator (LASSO) regression algorithm, Pearson correlation analysis, and univariable logistic analysis. Clinical features were selected with logistic regression analysis. Multivariable logistic regression analysis was conducted to develop three models for RTLI prediction in the training cohort: namely radiomics signature, clinical variables, and clinical-radiomics parameters. A radiomics nomogram was used and assessed with respect to calibration, discrimination, reclassification, and clinical application. RESULTS: The radiomics signature, composed of two radiomics features, was significantly associated with RTLI. The proposed radiomics model demonstrated favorable discrimination in both the training (AUC, 0.89) and the validation cohort (AUC, 0.92), outperforming the clinical prediction model (p < 0.05). Combining radiomics and clinical features, higher AUCs were achieved (AUC, 0.93 and 0.95), as well as a better calibration and improved accuracy of the prediction of RTLI. The clinical-radiomics model showed also excellent performance in predicting RTLI in different clinical-pathologic subgroups. CONCLUSION: A radiomics model derived from pretreatment MRI of the temporal lobe showed persuasive performance for predicting radiation-induced temporal lobe injury in nasopharyngeal carcinoma. KEY POINTS: • Radiomics features from pretreatment MRI are associated with radiation-induced temporal lobe injury in nasopharyngeal carcinoma. • The radiomics model shows better predictive performance than a clinical model and was similar to a clinical-radiomics model. • A clinical-radiomics model shows excellent performance in the prediction of radiation-induced temporal lobe injury in different clinical-pathologic subgroups.

Baseline MRI-based radiomics model assisted predicting disease progression in nasopharyngeal carcinoma patients with complete response after treatment.

BACKGROUND: Accurate pretreatment prediction for disease progression of nasopharyngeal carcinoma is key to intensify therapeutic strategies to high-risk individuals. Our aim was to evaluate the value of baseline MRI-based radiomics machine-learning models in predicting the disease progression in nasopharyngeal carcinoma patients who achieved complete response after treatment. METHODS: In this retrospective study, 171 patients with pathologically confirmed nasopharyngeal carcinoma were included. Using hold-out cross validation scheme (7:3), relevant radiomic features were selected with the least absolute shrinkage and selection operator method based on baseline T2-weighted fat suppression and contrast-enhanced T1-weighted images in the training cohort. After Pearson's correlation analysis of selected radiomic features, multivariate logistic regression analysis was applied to radiomic features and clinical characteristics selection. Logistic regression analysis and support vector machine classifier were utilized to build the predictive model respectively. The predictive accuracy of the model was evaluated by ROC analysis along with sensitivity, specificity and AUC calculated in the validation cohort. RESULTS: A prediction model using logistic regression analysis comprising 4 radiomics features (HGLZE_T2H, HGLZE_T1, LDLGLE_T1, and GLNU_T1) and 5 clinical features (histology, T stage, N stage, smoking history, and age) showed the best performance with an AUC of 0.75 in the training cohort (95% CI: 0.66-0.83) and 0.77 in the validation cohort (95% CI: 0.64-0.90). The nine independent impact factors were entered into the nomogram. The calibration curves for probability of 3-year disease progression showed good agreement. The features of this prediction model showed satisfactory clinical utility with decision curve analysis. CONCLUSIONS: A radiomics model derived from pretreatment MR showed good performance for predicting disease progression in nasopharyngeal carcinoma and may help to improve clinical decision making.

Using a machine learning approach to identify key prognostic molecules for esophageal squamous cell carcinoma.

BACKGROUND: A plethora of prognostic biomarkers for esophageal squamous cell carcinoma (ESCC) that have hitherto been reported are challenged with low reproducibility due to high molecular heterogeneity of ESCC. The purpose of this study was to identify the optimal biomarkers for ESCC using machine learning algorithms. METHODS: Biomarkers related to clinical survival, recurrence or therapeutic response of patients with ESCC were determined through literature database searching. Forty-eight biomarkers linked to recurrence or prognosis of ESCC were used to construct a molecular interaction network based on NetBox and then to identify the functional modules. Publicably available mRNA transcriptome data of ESCC downloaded from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets included GSE53625 and TCGA-ESCC. Five machine learning algorithms, including logical regression (LR), support vector machine (SVM), artificial neural network (ANN), random forest (RF) and XGBoost, were used to develop classifiers for prognostic classification for feature selection. The area under ROC curve (AUC) was used to evaluate the performance of the prognostic classifiers. The importances of identified molecules were ranked by their occurrence frequencies in the prognostic classifiers. Kaplan-Meier survival analysis and log-rank test were performed to determine the statistical significance of overall survival. RESULTS: A total of 48 clinically proven molecules associated with ESCC progression were used to construct a molecular interaction network with 3 functional modules comprising 17 component molecules. The 131,071 prognostic classifiers using these 17 molecules were built for each machine learning algorithm. Using the occurrence frequencies in the prognostic classifiers with AUCs greater than the mean value of all 131,071 AUCs to rank importances of these 17 molecules, stratifin encoded by SFN was identified as the optimal prognostic biomarker for ESCC, whose performance was further validated in another 2 independent cohorts. CONCLUSION: The occurrence frequencies across various feature selection approaches reflect the degree of clinical importance and stratifin is an optimal prognostic biomarker for ESCC.

The Role of Acupuncture in Postoperative Pain Management of Patients Undergoing Knee Arthroplasty Surgery: A Systematic Review and Meta-Analysis.

¼: Acupuncture after total knee arthroplasty (TKA) may decrease the incidence of postoperative nausea and vomiting (PONV). ¼: Acupuncture did not decrease visual analog scale (VAS) scores in the 0 to 48-hour interval but did decrease VAS scores at >48 hours after TKA. ¼: The heterogeneity of the studies prevented meta-analysis of opioid use with acupuncture after TKA; a systematic review demonstrated mixed results. ¼: Additional studies are needed to investigate opioid reduction with acupuncture after TKA.

Transcriptome Analysis of the Regulatory Mechanism of FoxO on Wing Dimorphism in the Brown Planthopper, Nilaparvata lugens (Hemiptera: Delphacidae).

The brown planthopper (BPH), Nilaparvata lugens, can develop into either short-winged (SW) or long-winged (LW) adults according to environmental conditions, and has long served as a model organism for exploring the mechanisms of wing polyphenism in insects. The transcription factor NlFoxO acts as a master regulator that directs the development of either SW or LW morphs, but the underlying molecular mechanism is largely unknown. Here, we microinjected SW-destined morphs with double stranded-RNA (dsRNA) targeting NlFoxO (dsNlFoxO) to change them into LW-winged morphs. In parallel, SW-destined morphs microinjected with dsRNA targeting the gene encoding green fluorescence protein (dsGfp) served as a negative control. The forewing and hindwing buds of 5th-instar nymphs collected at 24, 36, and 48 h after eclosion (hAE) were used for RNA sequencing. We obtained a minimum of 43.4 million clean reads from forewing and hindwing buds at a single developmental time. Differentially expressed genes (DEGs) were significantly enriched in various Gene Ontology (GO) terms, including cellular process, binding, and cell part. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis showed that up-regulated genes in dsNlFoxO-treated forewing and hindwing buds were largely associated with the cell cycle and DNA replication. Furthermore, most up-regulated genes displayed higher expression at 24-, and 36-hAE relative to 48 hAE, indicating that wing cells in LW-destined wings might actively proliferate during the first 36 h in 5th-instar nymphs. Our findings indicated that LW development in BPH was likely dependent on the duration of cell proliferation in the 5th-instar stage, which sheds light on the molecular basis of wing polymorphism in insects.

Thiophene donor for NIR-II fluorescence imaging-guided photothermal/photodynamic/chemo combination therapy.

Organic fluorophores/photosensitizers have been widely used in biological imaging and photodynamic and photothermal combination therapy in the first near-infrared (NIR-I) window. However, their applications in the second near-infrared (NIR-II) window are still limited primarily due to low fluorescence quantum yields (QYs). Here, a boron dipyrromethene (BDP) is created as a molecularly engineered thiophene donor unit with high QYs to the redshift. Thiophene insertion initiates substantial redshifts of the absorbance as compared to its counterparts in which iodine is introduced. The fluorescent molecule can be triggered by an NIR laser with a single wavelength, thereby producing emission in the NIR-II windows. Single NIR laser-triggered phototherapeutic nanoparticles (NPs) are developed by encapsulating the BDP and the chemotherapeutic drug docetaxel (DTX) by using a synthetic amphiphilic poly(styrene-co-chloromethyl styrene)-graft-poly(ethylene glycol) functionalized with folic acid (FA). These BDP-T-N-DTX-FA NPs not only show superior solubility and high singlet oxygen QY (ΦΔ=62%) but also demonstrate single NIR laser-triggered multifunctional characteristics. After intravenous administration of the NPs into 4T1 tumor-bearing mice, the accumulation of the NPs in the tumor showed a high signal-to-background ratio (11.8). Furthermore, 4T1 tumors in mice were almost eradicated by DTX released from the BDP-T-N-DTX-FA NPs under single NIR laser excitation and the combination of photodynamic therapy (PDT) and photothermic therapy (PTT). STATEMENT OF SIGNIFICANCE: The application of organic photosensitizers is still limited primarily due to low fluorescence quantum yields (QYs) in the second near-infrared (NIR-II) window. Here, a boron dipyrromethene (BDP) as a molecularly engineered thiophene donor unit with high QYs to the redshift is created. Phototherapeutic nanoparticles (NPs) are developed by encapsulating the BDP and docetaxel (DTX) using a synthetic amphiphilic poly(styrene-co-chloromethyl styrene)-graft-poly(ethylene glycol) functionalized with folic acid (FA). These BDP-T-N-DTX-FA NPs not only show high singlet oxygen QY (ΦΔ=62%) but also demonstrate single NIR laser-triggered multifunctional characteristics and a high signal-to-background ratio (11.8). Furthermore, 4T1 tumors in mice were almost eradicated by DTX released from the BDP-T-N-DTX-FA NPs under single NIR laser excitation and the PDT/PTT combination therapy.

Vestigial mediates the effect of insulin signaling pathway on wing-morph switching in planthoppers.

Wing polymorphism is an evolutionary feature found in a wide variety of insects, which offers a model system for studying the evolutionary significance of dispersal. In the wing-dimorphic planthopper Nilaparvata lugens, the insulin/insulin-like growth factor signaling (IIS) pathway acts as a 'master signal' that directs the development of either long-winged (LW) or short-winged (SW) morphs via regulation of the activity of Forkhead transcription factor subgroup O (NlFoxO). However, downstream effectors of the IIS-FoxO signaling cascade that mediate alternative wing morphs are unclear. Here we found that vestigial (Nlvg), a key wing-patterning gene, is selectively and temporally regulated by the IIS-FoxO signaling cascade during the wing-morph decision stage (fifth-instar stage). RNA interference (RNAi)-mediated silencing of Nlfoxo increase Nlvg expression in the fifth-instar stage (the last nymphal stage), thereby inducing LW development. Conversely, silencing of Nlvg can antagonize the effects of IIS activity on LW development, redirecting wing commitment from LW to the morph with intermediate wing size. In vitro and in vivo binding assays indicated that NlFoxO protein may suppress Nlvg expression by directly binding to the first intron region of the Nlvg locus. Our findings provide a first glimpse of the link connecting the IIS pathway to the wing-patterning network on the developmental plasticity of wings in insects, and help us understanding how phenotypic diversity is generated by the modification of a common set of pattern elements.